The long-term objective of this case-control study is the identification of environmental risk factors in congenital heart disease (CHD) in order to make possible the reduction of the occurrence of this major birth defect. This is a condinuing application to follow 3 years of field interviews on 960 families of infants with CHD and 1250 control families. The ongoing study is the first detailed epidemiologic study of CHD and is made possible through the joint efforts of five pediatric cardiology centers and 52 regional hospitals which provide access to 90,000 annual births. Preliminary analyses of the initial 1 1/2 year data on 530 cases and 700 controls have yielded findings which suggest genetically vulnerable subpopulations and the possible etiologic role of certain drugs, personal, home and occupational exposures acting as single or as interactive risk factors. Suspect occurrences and exposures are infrequent and confined to subsets of the CHD population so that statistical power can be derived only with a much larger case collection. Continuation of the case-control study to a total of 1,800 cases and 2,500 controls is requested. Concurrent with the field interviews analytic methods will be developed to identify constellations of factors predictive of CHD risks. Final analyses will result in recommendations concerning the identification of vulnerable families and the potential interventions on environmental risk factors. New etiologic hypotheses arising from this work will direct further use of epidemiologic research methods in the study of birth defects.